Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase

After multiple studies that have shown health benefits of the Mediterranean diet, researchers have now described a mechanism which may explain these benefits. The Mediterranean diet combines high consumption of unsaturated fats with vegetables abundant in nitrite and nitrate (olive oil and fish, combined with leafy greens). Although the Mediterranean diet is rich in fats that might promote cardiovascular disease, it appears to protect against hypertension and associated risks. In PNAS it is described how this type of diet may protect mice from hypertension.

The researchers directed their attention to nitro fatty acids, which are generated from the reaction of unsaturated fatty acids with nitrogen species, in an attempt to learn how they can lower blood pressure. These reactive lipids bind to and inhibit the enzyme soluble epoxide hydrolase (sEH), which causes vasodilation and a decrease in blood pressure.

To determine whether inhibition of sEH is sufficient to lower blood pressure in vivo, the authors generated mutant mice whose sEH enzyme was resistant to nitro fatty acid inhibition. A nitro fatty acid inhibitor of sEH that reduced blood pressure in wild-type mice had no effect on blood pressure in mice carrying the mutation. The inhibitor protected the hearts of wild-type mice from hypertrophy in a mouse model of hypertension, while sEH inhibition-resistant mutants were not protected.

When mice were fed certain nitro fatty acid precursors found in the Mediterranean diet, sEH was inhibited in wild-type but not mutant mice. Thus, protection from hypertension as provided by the Mediterranean diet is mediated by nitro-fatty acid-dependent inhibition of soluble epoxide hydrolase.

According to the authors, these findings might provide an explanation for the cardiovascular benefits of the Mediterranean diet whereby unsaturated fatty acids from olive oil or nuts combine with nitrite products from leafy greens to raise levels of nitro fatty acids, which lower blood pressure by inhibiting sEH.